Jun 28 2005
A tetracycline antibiotic, doxycycline, has been successfully used to treat a wide-range of bacterial infections. In addition to its effects as an antibiotic, doxycycline has other actions as a drug and, in laboratory studies with animals and with human tissue, can inhibit the degradation of cartilage in a way that could be useful for the treatment of osteoarthritis (OA). OA is a common form of arthritis associated with pain and disability related to the breakdown of cartilage, the tissue in the joint that absorbs shock and promotes smooth movement
On the strength of preclinical evidence, a team of rheumatologists affiliated with six clinical research centers across the United States conducted the first long-term clinical trial to determine the benefits of doxycycline in the treatment of OA--particularly, OA of the knee. Their findings, featured in the July 2005 issue of Arthritis & Rheumatism, suggest that doxycycline may slow the progression of joint damage and point to the need for further research into the drug's effect on the signs and symptoms of this disease.
For the trial, the team recruited 431 overweight women between the ages of 45 and 64 with moderately advanced OA in one knee. The subjects were randomly assigned to receive either 100 milligrams of doxycycline or a placebo twice a day for 30 months. At baseline, the 2 treatment groups were roughly equal with respect to all demographic variables, body mass index, and types of drugs taken for pain, as well as for the x-ray severity of OA in the affected knee and the level of knee pain and functional impairment. OA progression was assessed by measuring joint space narrowing in the medial tibiofemoral compartment through X-rays obtained at baseline, 16 months and 30 months. Severity of joint pain was assessed every 6 months after a washout period of all nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics.
71 percent of the subjects completed the treatment protocol. Radiographs were obtained from 85 percent of all subjects at 30 months. After 16 months of treatment, the mean loss of joint space width in the diseased knee in the doxycycline group was 40 percent less than in the placebo group. After 30 months, it was 33 percent less. Yet, despite significantly slowing disease progression, doxycycline did not reduce the severity of joint pain. However, mean pain scores at baseline were low in both treatment groups, leaving only limited opportunity to demonstrate improvement in joint pain. On the other hand, the drug significantly reduced the frequency with which subjects reported increases in knee pain 20 percent or greater than the level of pain they had at their previous semi-annual visit.
Notably, doxycycline seemed to have no effect on joint space narrowing or pain in the relatively disease-free knee. In both knees in both treatment groups, the rate of joint space narrowing was more than twice as rapid in subjects who reported frequent increases in pain than in those with a stable pain score. "Joint pain may serve as an indicator of synovitis that leads to cartilage destruction," observes the study's leading author, Kenneth D. Brandt, M.D.
Throughout the trial, fewer than 5 percent of all subjects reported side effects. In general, doxycycline seemed to be well tolerated. Subjects in the active treatment group experienced the unexpected side benefits of fewer urinary tract and upper respiratory tract infections than their placebo counterparts.
In conclusion, in this study, doxcycyline showed benefits in slowing the rate of joint space narrowing in knees with established OA. Whether this drug has any value in the early treatment and symptomatic management of OA, however, will require further investigation.